Hematological malignancies

• Laboratory diagnosis of haematological malignancies

  1. FBC, differential count, and smear review

  2. Bone marrow aspirate and trephine biopsy

  3. Smear findings may indicate specific diagnosis or suggest differential diagnosis

  4. Rapid provisional diagnosis in medical emergencies like Acute promyelocytic leukaemia
• The hierarchy of the haemopoietic system

  • Haemopoietic stem cells capable of self-renewal, proliferation, and giving rise to all haemopoietic lineages
  • Differentiation from HSC to lineage-restricted mature cells
• Molecular basis of leukaemias and lymphomas

  • Clonality: Malignancies arise from a single cell
  • Genetic mutations in susceptible cells
  • Clonal evolution with additional mutations providing survival advantage
  • Different malignancies have mutations affecting different pathways
  • Myeloid malignancies arise from oncogenic mutations in stem cells/early progenitors
  • Lymphoid malignancies arise from maturing lymphoid cells with oncogenic mutations during antigen receptor gene rearrangement
• Acute Leukaemias


  • Heterogeneous group of diseases varying in morphology, immunophenotype, cytogenetic, and molecular genetic abnormalities
  • Leukaemic transformation at the level of haemopoietic stem cell or early progenitors
  • Accumulation of primitive blasts leading to marrow failure and organ infiltration
• Cell types in the haemopoietic system

  • Haemopoietic stem cells
  • Immature progenitor cells
  • Colony forming unit granulocyte erythroid macrophage and megakaryocyte (CFU-GEMM)
  • Bipotent progenitors e.g. CFU-GM
  • Restricted progenitors CFU-G, CFU-M
  • Mature lineage-restricted cells
• Myeloproliferative neoplasms


  Clonal HSC disorders characterized by the increased proliferation of one of the granulocytic lineages
• Chronic Myeloid leukaemia

  Increased tyrosine kinase activity results in activation of proteins in signal transduction pathways involved in cell growth, survival, and inhibition of apoptosis affecting the granulocytic cell line predominantly
• Other organ infiltration can occur
• Acute leukaemias

  • Acute promyelocytic leukaemia
  • Myeloproliferative neoplasms
  • Polycythaemia vera
  • Essential thrombocythaemia
  • Chronic myeloid leukaemia
  • Chronic neutrophilic leukaemia
  • Chronic eosinophilic leukaemia
  • Myelofibrosis
• Chronic Myeloid leukaemia

  Defined by an acquired reciprocal translocation between the ableson gene on chromosome 9 and the break point cluster region gene on chromosome 22 resulting in the Ph chromosome. The BCR-ABL1 fusion gene encodes a protein with tyrosine kinase activity
• Chronic Myeloid leukaemia

  BCR-ABL1 tyrosine kinase inhibitors (TKI) such as Imatinib prevent the fusion protein from phosphorylating its substrates and control the disease. Drug resistance can develop through the acquisition of mutations requiring the use of second and third generation TKIs e.g. nilotinib, dasatinib. Excellent prognosis with 80-95% 5-year survival rates, with a small percentage progressing to acute leukaemia
• Result of accumulation of a clone of cells


  Primitive cells referred to as blasts fill the marrow cavity and result in marrow failure
• Myelodysplastic syndromes (MDS)

  Common in the elderly and slowly progressive, characterised by ineffective haemopoiesis resulting in hypercellular marrow but peripheral blood cytopenias. Present with symptoms of anaemia, neutropenia, and/or thrombocytopenia. FBC and differential count often reveal pancytopenia with a macrocytic anaemia. Genetic abnormality must be present
• Lymphomas/lymphoproliferative disorders

  • Mature B cell neoplasms
  • Mature T-cell and NK-cell leukaemias
• Chronic lymphocytic leukaemia (CLL)


  Is a monoclonal disorder characterised by a progressive proliferation and accumulation of mature yet functionally defective B-lymphocytes. The term "chronic" comes from the fact that this disease typically progresses more slowly than other types of leukaemia. CLL is the most common form of leukaemia found in adults in Western countries, median age is 70 years. Onset is insidious, often found incidentally, FBC performed for another reason. Clinical features if present: lymphadenopathy, generalised and symmetrical, splenomegaly, anaemia, thrombocytopenia (autoimmune, marrow infiltration hypersplenism) Infections (hypogammaglobulinaemia)
• Types of lymphoma

  • Plasma cell neoplasms
  • Mature T-cell and NK-cell leukaemias
  • T-prolymphocytic leukaemia
  • T cell Large granular lymphocytic leukaemia
  • Adult T-cell leukaemia/lymphoma
  • Sezary syndrome
  • Mycosis fungoides
  • Aggressive NK-cell leukaemia
  • Anaplastic large cell lymphoma
  • Peripheral T-cell lymphoma, NOS
  • Hodgkin lymphoma
  • Non-Hodgkin lymphomas
  • Chronic lymphocytic leukaemia (CLL)
  • Burkitt lymphoma
• Burkitt lymphoma


  Aggressive lymphoma of B lymphocytes. Common in children. Presents with rapidly enlarging lymph nodes and tumour masses involving multiple sites in the chest and abdomen including the GIT, gonads, kidneys, breasts. B symptoms are often present. High risk for (CNS) involvement. Three types: endemic, sporadic and immunodeficiency-associated (HIV). Association with EBV infection, especially endemic form. Morphology: Monomorphic medium-sized cells
• Lymphadenopathy (LAD)


  The term is used to represent a change in size of a lymph node. Lymphadenopathy may be generalised or localised. A lymph node >1cm in diameter is considered enlarged
• Clinical approach to Lymphadenopathy (LAD)

  1. Examination of LAD location and extent

  2. Palpate accessible nodes in a systemic fashion starting with lymph nodes in the neck. Assess all cervical lymph node chains, axillary, epitrochlear, inguinal, femoral, and popliteal fossa

  3. Imaging should be done for central nodes which are not accessible on examination especially when there is generalised lymphadenopathy or symptoms of compression etc. Assess for intrathoracic nodes including hilar/mediastinal and intra-abdominal
• Chronic lymphocytic leukaemia (CLL) Diagnostic criteria


  ≥ 5 x 10⁹/L monoclonal B cells in the PB with characteristic morphology and immunophenotype. Chromosomal abnormalities 11q23 deletion, Trisomy 12, 13q14.3 deletion, 17p13 deletion (TP53)
• Causes of lymphadenopathy

  • Viral: Infectious mononucleosis, measles, rubella, HIV
  • Bacterial: Tuberculosis, Syphilis, salmonella
  • Fungal: Histoplasma
  • Protozoal: toxoplasmosis
  • Other inflammatory conditions: Rheumatoid arthritis, sarcoidosis, SLE
  • Malignant conditions: Lymphomas (Hodgkin lymphoma and non-Hodgkin lymphomas), Leukaemias (ALL), Carcinomas (rare)
• Chromosome translocation t(8;14) involved in pathogenesis

  MYC and IgH genes
• Commonly involved bones in endemic Burkitts lymphoma


  • Jaw and facial bones
• Patients with rapidly enlarging lymph nodes and tumour masses involving multiple sites in the chest and abdomen including the GIT, gonads, kidneys, breasts often have B symptoms
• Morphology of lymphoma cells

  Monomorphic medium-sized cells with deeply basophilic cytoplasm and cytoplasmic vacuolation
• Association with EBV infection, especially in the endemic form
• Types of lymphoma

  • Endemic
  • Sporadic
  • Immunodeficiency-associated (HIV)
• High risk for (CNS) involvement
• Diagnostic markers for Hodgkin lymphoma

  • CD10
  • CD20
  • CD19
  • Kappa or lambda
• Bulky mediastinal disease in Hodgkin lymphoma may result in symptoms like a persistent cough, shortness of breath, pleural effusion, or superior vena cava syndrome
• Classic diagnostic cells for Hodgkin lymphoma are malignant B cells called Reed Sternberg Cells
• 20% of Hodgkin lymphoma patients present with localized disease and 70% with advanced stage disease with B symptoms
• Peak incidence of Hodgkin lymphoma is in young adults
• Patients with Hodgkin lymphoma usually present with asymmetrical peripheral lymphadenopathy
• Cytopenias may be present in Hodgkin lymphoma patients with marrow involvement
• Stage determines the intensity of treatment for Hodgkin lymphoma
• Hodgkin lymphoma is commonly associated with EBV infection
• Plasma cell dyscrasias result from a clone of immunoglobulin-secreting terminally differentiated B cells
• Hodgkin lymphoma is curable in over 80% of cases with radiotherapy and chemotherapy
• Plasma cell dyscrasias secrete a monoclonal immunoglobulin known as an M protein